DNA N6-methyladenine involvement and regulation of hepatocellular carcinoma development.

DNA N6-methyladenine (6 mA) is a new type of DNA methylation identified in various eukaryotic cells. However, its alteration and genomic distribution features in hepatocellular carcinoma (HCC) remain elusive. In this study, we found that N6AMT1 overexpression increased HCC cell viability, suppressed apoptosis, and enhanced migration and invasion, whereas ALKBH1 overexpression induced the opposite effects. Further, 23,779 gain-of-6 mA regions and 11,240 loss-of-6 mA regions were differentially identified in HCC tissues. The differential gain and loss of 6 mA regions were considerably enriched in intergenic regions. Moreover, 7% of the differential 6 mA modifications were associated with tumors, with 60 associated with oncogenes and 57 with tumor suppressor genes (TSGs), and 17 were common to oncogenes and TSGs. The candidate genes affected by 6 mA were filtered by gene ontology (GO) and RNA-seq. Using quantitative polymerase chain reaction (qPCR), BCL2 and PARTICL were found to be correlated with DNA 6 mA in certain HCC processes.

Stent placement with iodine-125 seeds strand effectively extends the duration of stent patency and survival in patients with unresectable malignant obstructive jaundice.

Background: This study aimed to compare the treatment outcomes and safety between stent placement with or without Iodine-125 (125I) seeds strand for patients with unresectable malignant obstructive jaundice (MOJ).Methods: A total of 84 patients with unresectable MOJ treated in our hospital were retrospectively included and divided into the stent group (n = 54) undergoing biliary stent placement and the stent + seeds group (n = 30) receiving stent placement with 125I seeds strand. The therapeutic outcome, postoperative complications, duration of patient survival and stent patency were compared between groups. Kaplan-Meier survival analysis was performed to compare the duration of patient survival and stent patency between groups. Cox-regression analysis was performed to investigate predictive factors for disease-free survival and overall survival.Results: The stent + seeds group had significantly longer duration of patency (231.57 ± 256.54 vs. 110.37 ± 120.52) and overall survival (310.57 ± 330.54 vs. 173.15 ± 219.40) than the stent group (both p < .05). In addition, Kaplan-Meier survival analysis confirmed that the stent + seeds group had longer duration of patency (log-rank test, p = .001) and higher overall survival rate (log-rank test, p = .020) than the stent group. Furthermore, Cox-regression analysis demonstrated that treatment methods was an independent factor associated with disease-free survival (HR: 0.36, 95% CI: 0.19-0.70; p = .003) and overall survival (HR: 1.01, 95% CI: 1.00-1.01; p < .001).Conclusion: The stent placement with 125I seeds strand can significantly improve the primary patency rate and overall survival time in MOJ patients.

Uterine artery embolization combined with methotrexate in the treatment of cesarean scar pregnancy: results of a case series and review of the literature.

PURPOSE: To explore the clinical value of uterine artery embolization (UAE) combined with methotrexate in the treatment of cesarean scar pregnancy (CSP) before and after uterine curettage. MATERIALS AND METHODS: From August 2009 to April 2012, 15 patients with CSP treated with UAE (before or after uterine curettage) were analyzed retrospectively. Eleven subjects with a definite diagnosis of CSP were offered preventive UAE combined with methotrexate before uterine curettage. The other four patients, who were misdiagnosed as having an intrauterine pregnancy, were treated with emergency UAE for uncontrollable massive hemorrhage after uterine curettage. Clinical data, treatment sequence, and outcome were analyzed, and a brief review of the published literature summarizing UAE in the treatment of CSP was performed. RESULTS: Eleven patients with definite CSP received preventive UAE combined with methotrexate followed by uterine curettage, and CSP was resolved successfully without hysterectomy. In the four misdiagnosed patients, three were treated successfully with emergency UAE. The other patient underwent uterine curettage and emergency UAE followed by repeat curettage, but hysterectomy was performed because of continued severe hemorrhage. CONCLUSIONS: Based on a small number of patients, it appears that UAE may be an effective means of treating CSP, including treatment in an emergency setting. Further study is required before the safety and effectiveness of UAE can be confirmed.

[Clinical study of percutaneous transhepatic intrahepatic portosystemic shunt].

OBJECTIVE: To introduce an innovative procedure for portal hypertension with preliminary results and assess the technical feasibility and efficacy of portosystemic shunt creation through percutaneous transhepatic approach with its potential clinical significance. METHODS: Between November 2009 and January 2011, 8 patients with complicated portal hypertension underwent percutaneous transhepatic intrahepatic portosystemic shunt (PTIPS). The severity of liver disease was Child's A (n = 2), Child's B (n = 3) and Child's C (n = 3). Under fluoroscopic guidance, portal vein (PV) was punctured with a 22-gauge Chiba needle. A 0.018-inch guidewire was advanced through the needle into PV lumen. The needle was exchanged and a 7-French sheath inserted over the wire. Then retrohepatic inferior vena cava (RIVC) or hepatic vein (HV) was punctured with a 20-gauge, 20-cm Chiba needle through sheath. Another 0.018-inch guidewire was advanced through the needle into right internal jugular vein and then snared out of body. A 0.035-inch, 260-cm-long stiff shaft wire was then introduced through the transjugular sheath and manipulated into main portal vein (MPV) and then into superior mesenteric vein (SMV). Afterward the PTIPS procedure was completed in the standard transjugular fashion. RESULTS: The procedure was technically successful in all patients. And effective portal decompression and free antegrade shunt flow were achieved. The mean portal pressure gradient decreased from 31.0 ± 4.3 to 18.9 ± 2.7 mm Hg before and after PTIPS creation respectively and the difference was significant statistically (P < 0.01). Among 8 patients, 1 developed hepatic coma and died after 5 days while the other 7 patients survived. The median follow-up period was 9 months (range: 2 - 20). Among 5 patients with PTIPS created for bleeding varices, no recurrent bleeding occurred during the follow-up period. For the patient with diffuse portal vein thrombosis, the clinical symptoms disappeared after PTIPS and computed tomography (CT) showed the shunt was occluded after 4 months. One patient with refractory ascites had a recurrence of abdominal distention after 2 months. There was a stenotic shunt on CT. Cure was achieved by replanting a stent in MPV. CONCLUSION: PTIPS is both safe and effective for the treatment of portal hypertension with exceptionally challenging anatomy. It is an available supplement for transjugular intrahepatic portosystemic shunt.

Degradation of iopamidol by UV365/NaClO: Roles of reactive species, degradation mechanism, and toxicology.

The degradation of iopamidol (IPM) was investigated using a UV365/NaClO system. The reactive species (HO·, ClO·, ozone, Cl·, and Cl2-·) in the system were identified, and the changing trends of the percentage contributions of these reactive species to IPM removal under various conditions were systematically evaluated. The results showed that ClO· and HO· played the most significant roles in the apparent pseudo-first-order rate constants of IPM degradation (kobs, min-1) in the control experiment, and their percentage contributions to kobs were 41.31% and 34.45%, respectively. In addition, Cl· and Cl2-· together contributed 22% to the kobs. Furthermore, the contribution of ozone to the IPM removal could be neglected. The concentrations of these species increased significantly when the concentration of NaClO was increased from 50 µM to 200 µM, while the percentage contribution of ClO· to kobs was greatly increased. The concentrations and percentage contributions of HO· and ClO· decreased significantly as the solution pH increased from 5 to 9, with Cl2-· playing a greater role in the degradation of IPM under alkaline conditions. While Cl- or HCO3-/CO32- significantly promoted the generation of Cl2-· or CO3-·, neither had an obvious effect on kobs, suggesting that Cl2-· and CO3-· should have a certain reactivity with IPM. Compared with that of Cl2-·, the percentage contribution of ClO· and Cl· to kobs was more likely to be inhibited by NOM. In addition, the organic and inorganic oxidation products of IPM were detected. The oxidation mechanisms of IPM degradation in the UV365/NaClO system, such as the H-extraction reaction, deiodination, substitution reaction, amide hydrolysis, and amine oxidation, were proposed according to the obtained 15 organic products. No effect on acute toxicity towards Vibrio fischeri and Photobacterium phosphoreum was detected during the oxidation of IPM by the UV365/NaClO system. Furthermore, the engineering feasibility of the oxidation system was demonstrated, by the effective degradation of IPM in actual water. However, HOI rapidly accumulated during the removal of IPM in the UV365/NaClO system, which poses certain environmental risks and will needs to be investigated.

[Application value of diffusion-weighted imaging in ischemic-type biliary lesions after liver transplantation].

OBJECTIVE: To discuss the application values of DWI (diffusion-weighted imaging) and ADC (apparent diffusion coefficient) on ischemic-type biliary lesions (ITBL) after orthotopic liver transplantation. METHODS: According to whether there was ITBL after liver transplantation or not, 46 cases of liver transplantation were selected and divided into 2 groups on the basis of PTC (percutaneous transhepatic cholangiography) or ERCP (endoscopic retrograde cholangiopancreatography) examination, pathology or clinical follow-up data: ITBL group (n = 29) and no ITBL group (C group, n = 17). The ADC value was measured for right lobe of graft liver parenchyma (b value = 600 s/mm(2)). And the signal of biliary system of graft on DWI and biliary tract on MRCP were analyzed. RESULTS: (1) The ADC values of liver graft were (1.456 ± 0.286) × 10(-3) mm(2)/s and (1.716 ± 0.391) × 10(-3) mm(2)/s in ITBL and C groups respectively. The difference in ADC value was significant between two groups (P = 0.015); (2) the incidence of increased signal of bile duct on DWI was 82.8% (24/29) and 5.9% (1/17) for ITBL and C groups respectively. The lesion was located in porta hepatis and intrahepatic small bile duct was seen in 17 of 24 patients (70.8%) in ITBL group. The difference was significant in signal of bile ducts between ITBL and C groups (P < 0.001). Twenty-one cases with sludge on DWI in ITBL group had hyperintensity, isointensity or hypointensity. There was no abnormal signal in the lumen of bile duct in C group. CONCLUSION: The major sign of ITBL is a hyperintensity of porta hepatis and small bile ducts on DWI. And the ADC value of graft liver parenchyma decreases. These reflect the pathological changes to an extent and may be an effective and sensitive monitoring tool of early ITBL. DWI is a novel, non-invasive, simple and practical method in the diagnosis and differential diagnosis of ITBL after liver transplantation.

Exosome-mediated miRNA delivery promotes liver cancer EMT and metastasis.

The deregulation of exosomal microRNAs (miRNAs) plays an important role in the progression of hepatocarcinogenesis. In this study, we highlight exosomes as mediators involved in modulating miRNA profiles in liver cancer cells after induction of the epithelial-mesenchymal transition (EMT) and metastasis. Initially, we induced EMT in a hepatocellular carcinoma cell (HCC) line (Hep3B) by stimulation with transforming growth factor-ß (TGF-ß) and confirmed by western blot detection of EMT markers such as vimentin and E-cadherin. Exosomes were then isolated from the cells and identified by nanoparticle tracking analysis (NTA). The isolated exosomal particles from unstimulated Hep3B cells (Hep3B exo) or TGF-ß-stimulated EMT Hep3B cells (EMT-Hep3B exo) contained higher levels of exosome marker proteins, CD63 and TSG101. After incubation with EMT-Hep3B exo, Hep3B cell proliferation increased. EMT-Hep3B exo promoted the migration and invasion of Hep3B and 7721 cells. High-throughput sequencing of miRNAs and mRNA within the exosomes showed 119 upregulated and 186 downregulated miRNAs and 156 upregulated and 166 downregulated mRNA sequences in the EMT-Hep3B exo compared with the control Hep3B exo. The most differentially expressed miRNAs and target mRNA sequences were validated by RT-qPCR. Based on the known miRNA targets for specific mRNA sequences, we hypothesized that GADD45A was regulated by miR-374a-5p. Inhibition of miR-374a-5p in Hep3B cells resulted in exosomes that inhibited the proliferation, migration, and invasion of HCC cells. These results enhance our understanding of metastatic progression of liver cancer and provide a foundation for the future development of potential biomarkers for diagnosis and prognosis of hepatic cancer.

[Multimodality interventional treatments for biliary complications after orthotopic liver transplantation: a preliminary study].

OBJECTIVE: To describe the technique, efficacy, and safety of multimodality interventional treatments for biliary complications after orthotopic liver transplantation (OLT). The core of multimodality interventional treatments is percutaneous transhepatic biliary drainage (PTBD). METHODS: From January 2006 to May 2008, seventy-two patients with biliary complications afte OLT were closed in our study. On the basis of the cholangiographic appearance, patients were classified into 4 groups: anastomotic biliary strictures (n = 19), hilar biliary strictures (n = 16), multifocal/diffuse biliary strictures (n = 31), and anastomotic biliary fistulae (n = 6). All patients were treated in our hospital, including PTBD only in 6 patients, PTBD combined with balloon dilation in 50 patients, balloon dilation and plastic stent implantation in 10 patients, balloon dilation and metallic stent implantation in 6 patients. Their data were analyzed retrospectively, including serum hemobilirubin, cholangiographic appearance and complications. RESULTS: PTBD were successful in all cases. The clinical symptoms improved or eliminated were observed in 66 cases, the effective rate was 91.7% (66/72). Among 72 patients, 26 patients were free of drainage tube, 8 patients underwent second PTBD for the obstruction of biliary stents, and 38 patients maintained drainage tube for long-term. In 66 patients with biliary obstruction, the direct bilirubin was (145 +/- 106) micromol/L before treatments and 76 micromol/L +/- 59 micromol/L one month after PTBD (t = 3.78, P < 0.001). The rate of biliary tract infection was 14.3% and 43.8% respectively with the tip of drainage tube placed in biliary duct and in duodenum. There was a significantly statistical difference between these two items (chi(2) = 4.886, P = 0.027). CONCLUSION: PTBD combined with balloon dilation and biliary stent implantation is a effective therapeutic modality for biliary complications after OLT, which can improve patients' clinical symptoms, elevate patients' quality of life. The tip of drainage tube being placed in biliary duct can decrease the rate of biliary tract infection significantly.

Transarterial chemoembolization with pirarubicin-eluting microspheres in patients with unresectable hepatocellular carcinoma: Preliminary results.

PURPOSE: To present the early results of pirarubicin-eluting microsphere transarterial chemoembolization (PE-TACE) for patients with unresectable hepatocellular carcinoma (HCC). MATERIALS AND METHODS: We retrospectively analyzed 55 consecutive patients with HCC who received PE-TACE between April 1, 2015 and August 30, 2016. The complication rate, tumor response rate, progression-free survival (PFS), and overall survival (OS) were analyzed. RESULTS: Adverse events were generally mild and included abdominal pain and fever, although a major complication was reported in 1 patient (1.8%). During a median follow-up of 10.0 months (range, 3.0-24.0 months), 14 patients (25.5%) achieved a complete tumor response, 25 (45.5%) had a partial response, 9 (16.4%) showed stable disease, and 7 (12.7%) had disease progression. The 1-month overall response rate was 70.9%, and the local tumor response rate was 89.0%. The 1-month tumor response rate was 100% for Barcelona Clinic Liver Cancer (BCLC) stage A or B disease and 62.8% for BCLC stage C disease. The median PFS was 6.1 months (95% confidence interval [95%CI], 3.4-8.8 months; range, 1.0-24.0 months). The median OS was 11.0 months (95%CI, 7.1-14.9 months; range, 2.0-24.0 months). Kaplan-Meier analysis (log-rank test) found significant differences in OS between patients grouped by tumor number (P = 0.006), tumor size (P = 0.035), and Eastern Cooperative Oncology Group (ECOG) score (P = 0.005). The tumor number (1 vs. ≥2) was the only factor independently associated with OS (hazard ratio [HR], 2.867; 95%CI, 1.330-6.181; P = 0.007). CONCLUSIONS: PE-TACE for unresectable HCC may be safe, with favorable tumor response rates and survival time, especially in patients with a single large tumor. Longer follow-up using a larger series is necessary to confirm these preliminary results.